Abstract Number: LPB0072
Meeting: ISTH 2021 Congress
Background: Platelet function can be “kidnaped” by cancer cells to support tumor growth; causing alterations in the delicate hemostatic equilibrium. This leads to a four-fold risk of thrombotic events in cancer patients, which in turn, portend poor prognosis. We previously demonstrated that anti-P2RY12 drugs inhibit thrombosis associated with cancer and formation of metastasis in pancreatic cancer models.
Aims: (1) To determine the expression of P2RY12 across different digestive cancers (colorectal and pancreatic) and demonstrate its effect in vitro.
(2) To characterize the effects of known antiplatelet drug clopidogrel (platelet P2RY12 inhibitor) on cancer associated thrombosis and cancer growth in vivo.
(3) To compare the effects of clopidogrel and aspirin in pancreatic cancer progression.
Methods: We used flow cytometry and immunohistochemistry; along with molecular biology techniques like RT-qPCR, and cDNA sequencing techniques to determine P2YR12 presence in primary tissue and cell lines. The effect of P2RY12 on cancer cell lines was determined using wound healing, proliferation tests and transwell culture. Syngeneic ectopic and orthotopic mouse cancer models using pancreatic cancer cell line PANC02, coupled with intravital microscopy.
Results: Various cancer cell lines express functional P2RY12, which when activated significantly increases cell migration and proliferation. Differential tumor P2RY12 expression could explain different pro-coagulation status of patients. Clopidogrel treatment resulted in better survival rates with smaller primary tumors and less metastasis than aspirin treatment. Clopidogrel was more effective than aspirin at dissolving spontaneous endogenous thrombi in our orthotopic cancer mouse model.
Conclusions: Pancreatic adenocarcinomas express P2RY12, which gives the tumor proliferative advantages. The power to slow cancer spread of P2RY12 inhibitors warrants further studies to include it in current pancreatic cancer treatment panels. Clopidogrel can be used to target and prevent Trousseau’s syndrome with fewer side effects than aspirin.
To cite this abstract in AMA style:Palacios Acedo AL, Mezouar S, Mege D, Crescence L, Dubois C, Panicot-Dubois L. Aspirin vs P2RY12-Inhibitors to Reduce Cancer Associated Thrombosis and Tumor Growth in Digestive Cancers [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/aspirin-vs-p2ry12-inhibitors-to-reduce-cancer-associated-thrombosis-and-tumor-growth-in-digestive-cancers/. Accessed February 29, 2024.
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